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Tumor Necrosis Factor Reduces Brain Tumor Growth by Enhancing Macrophage Recruitment and Microcyst Formation

Department of Oncology and Molecular Endocrinology, Laval University Hospital Research Center, Québec City, Québec, Canada

Requests for reprints: Luc Vallières, Department of Oncology and Molecular Endocrinology, Laval University Hospital Research Center, 2705 Laurier Boulevard, T3-67, Québec City, Québec, Canada G1V 4G2. Phone: 418-654-2296; Fax: 418-654-2761; E-mail: Luc.Vallieres{at}crchul.ulaval.ca.

Recent findings implicate macrophages and some of their secreted products, especially tumor necrosis factor (TNF), as tumor promoters. Inhibitors of these inflammatory components are currently regarded as potential therapeutic tools to block tumor progression. Here, we show that infiltrating macrophages represented a significant population of nonneoplastic cells within malignant gliomas, in which they were the exclusive producers of TNF. Contrary to the reported pro-oncogenic effects of TNF in other types of solid tumors, glioma-bearing mice deficient in TNF developed larger tumors and had reduced survival compared with their wild-type controls. Histologic examinations revealed that glioma volume was negatively correlated with the number of macrophages and small cavities called microcysts. Overall, our results support the concept that macrophages alter brain tumor development through a TNF-dependent process that culminates in the formation of microcysts. This raises the question of whether anti-inflammatory drugs, such as those commonly administrated to patients with brain cancer, could interfere with antitumor mechanisms.

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